Fluoride Exposure in Community Prevention Programmes for Oral Health Using Nail Clippings and Spot Urine Samples: A Systematic Review and Meta-Analysis.

Due to practical difficulties in quantifying fluoride exposure in populations, practical and accurate biomarkers can play a major role in the surveillance of fluoride. Among different fluoride biomarkers, spot urine and nail clippings have gained more attention due to their ease of acquisition. However, there is no robust consensus about the accuracy of these biomarkers for the estimation of fluoride exposure. This systematic review and meta-analysis aimed to synthesise evidence on the association between fluoride exposure and the fluoride concentration of spot urine and nail clippings. This review was conducted and reported using the PRISMA Statement. Nine databases (Medline, CINAHL, Web of Science, Scopus, ScienceDirect, Sage Journals Online, Campbell Collaboration, Cochrane Collaboration, and Embase); search engines (Google and Google Scholar); and grey literature were searched up to September 2022. All screening, data extraction, and quality assessments were conducted in duplicate. All experimental and observational research studies that reported the correlation between fluoride exposure and fluoride concentrations of spot urine and/or nail clippings were included. The Mixed-Methods Appraisal tool was used to assess the methodological quality of the included studies. A random effect meta-analysis was carried out to determine the relationship between fluoride exposure and fluoride concentration of biomarkers (i.e., spot urine and nail clippings). Forty-four studies met the inclusion criteria. A total of 694,578 participants were included in this review. Twenty-five studies were included in the meta-analysis. The primary meta-analysis showed a moderate correlation of 0.674 (95% confidence interval [CI]: 0.623-0.725, n = 25) between fluoride intake and fluoride concentration of spot urine and a strong correlation of 0.938 (95% CI: 0.520-1.355, n = 11) between fluoride intake and the fluoride concentration of nail clippings in all age groups. The findings of secondary meta-analyses showed a strong positive correlation between fluoride intake and fluoride/creatinine ratio of spot urine in children (0.929; 95% CI: 0.502-0.991; n = 2). In conclusion, spot urine and nail clippings have the potential to be employed as non-invasively obtained biomarkers in populations. However, due to the scarcity of high quality, relevant studies, more research is needed to establish the validity of these biomarkers.

Prolonged exposure to high fluoride levels during adolescence to adulthood elicits molecular, morphological, and functional impairments in the hippocampus.

Fluoride is added to water due to its anticariogenic activity. However, due to its natural presence in soils and reservoirs at high levels, it could be a potential environmental toxicant. This study investigated whether prolonged exposure to fluoride from adolescence to adulthood-at concentrations commonly found in artificially fluoridated water and in fluorosis endemic areas-is associated with memory and learning impairments in mice, and assessed the molecular and morphological aspects involved. For this endeavor, 21-days-old mice received 10 or 50 mg/L of fluoride in drinking water for 60 days and the results indicated that the increased plasma fluoride bioavailability was associated with the triggering of short- and long-term memory impairments after high F concentration levels. These changes were associated with modulation of the hippocampal proteomic profile, especially of proteins related to synaptic communication, and a neurodegenerative pattern in the CA3 and DG. From a translational perspective, our data provide evidence of potential molecular targets of fluoride neurotoxicity in the hippocampus at levels much higher than that in artificially fluoridated water and reinforce the safety of exposure to low concentrations of fluoride. In conclusion, prolonged exposure to the optimum fluoride level of artificially fluoridated water was not associated with cognitive impairments, while a higher concentration associated with fluorosis triggered memory and learning deficits, associated with a neuronal density reduction in the hippocampus.

Health risks associated with the production and usage of charcoal: a systematic review.

Charcoal production and utilisation are linked to various health issues and occupational hazards. However, to our knowledge, no systematic review has primarily focused on the health implications of charcoal production and its use while distinguishing charcoal from other solid fuels such as wood and coal. OBJECTIVES: This systematic review presents a synthesis of the evidence on the health risks associated with producing and using charcoal across the world. DESIGN: Systematic review using a systematic narrative synthesis approach. DATA SOURCES: MEDLINE (through Ovid interface), CINAHL, Embase, Web of Science, PsycINFO, Cochrane Library and SCOPUS, from inception to 26 February 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Peer-reviewed journal articles reporting empirical findings on the associations between charcoal usage/production and health parameters. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the quality of primary studies. RESULTS: Our findings showed that charcoal production and usage are linked with specific adverse health outcomes, including respiratory diseases (n=21), cardiorespiratory and neurological diseases (n=1), cancer (n=3), DNA damage (n=3), carbon monoxide (CO) poisoning (n=2), physical injury (n=2), sick house syndrome (n=1), unintentional weight loss and body mass index (BMI) reduction (n=2), increase in blood pressure (n=1) and CO death (n=1). Among the included articles that reported respiratory diseases (n=21), there was one case of asthma and tuberculosis and two cases of chronic obstructive pulmonary disease. CONCLUSIONS: This review links charcoal production/usage and some associated human health risks. These include respiratory diseases and other non-respiratory illnesses such as sick-building syndrome, cardiovascular diseases, DNA damage, CO poisoning and death, unintentional weight loss and BMI reduction, and physical injuries.

Human and environmental impacts of nanoparticles: a scoping review of the current literature.

Use of nanoparticles have established benefits in a wide range of applications, however, the effects of exposure to nanoparticles on health and the environmental risks associated with the production and use of nanoparticles are less well-established. The present study addresses this gap in knowledge by examining, through a scoping review of the current literature, the effects of nanoparticles on human health and the environment. We searched relevant databases including Medline, Web of Science, ScienceDirect, Scopus, CINAHL, Embase, and SAGE journals, as well as Google, Google Scholar, and grey literature from June 2021 to July 2021. After removing duplicate articles, the title and abstracts of 1495 articles were first screened followed by the full-texts of 249 studies, and this resulted in the inclusion of 117 studies in the presented review.In this contribution we conclude that while nanoparticles offer distinct benefits in a range of applications, they pose significant threats to humans and the environment. Using several biological models and biomarkers, the included studies revealed the toxic effects of nanoparticles (mainly zinc oxide, silicon dioxide, titanium dioxide, silver, and carbon nanotubes) to include cell death, production of oxidative stress, DNA damage, apoptosis, and induction of inflammatory responses. Most of the included studies (65.81%) investigated inorganic-based nanoparticles. In terms of biomarkers, most studies (76.9%) used immortalised cell lines, whiles 18.8% used primary cells as the biomarker for assessing human health effect of nanoparticles. Biomarkers that were used for assessing environmental impact of nanoparticles included soil samples and soybean seeds, zebrafish larvae, fish, and Daphnia magna neonates.From the studies included in this work the United States recorded the highest number of publications (n = 30, 25.64%), followed by China, India, and Saudi Arabia recording the same number of publications (n = 8 each), with 95.75% of the studies published from the year 2009. The majority of the included studies (93.16%) assessed impact of nanoparticles on human health, and 95.7% used experimental study design. This shows a clear gap exists in examining the impact of nanoparticles on the environment.

App-based oral health promotion interventions on modifiable risk factors associated with early childhood caries: A systematic review.

Background: Early childhood caries (ECC) is a preventable chronic disease. Parents' knowledge and attitudes toward oral healthcare have been associated with higher caries experience in their children. Mobile apps within the context of mHealth interventions are a potential tool for raising awareness and informing parents about their children's oral health. Objectives: The aim of this systematic review was to examine the effectiveness of mobile health apps, targeted at parents and caregivers, for the prevention of ECC. Data sources: A systematic search was carried out in five scientific databases; Embase, CINAHL, MEDLINE, PsycINFO and Web of Science. Study selection and data extraction: Original studies, delivering oral health interventions to parents of children <6 years via smartphones, were included. Both quantitative and qualitative findings from the included studies were extracted. Synthesis: A convergent segregated approach was used to integrate the quantitative and qualitative evidence, followed by side-by-side display and narrative synthesis. Results: Out of 5,953 retrieved articles, five met the inclusion criteria and were included in the review. Three articles reported quantitative findings, while two reported both quantitative and qualitative findings. Four studies reported that a mobile app can be an effective tool to improve the oral health knowledge of parents/caregivers, aiding them in incorporating good oral health habits into their children's daily routines. Conclusion: This review demonstrated that oral health promotion programs delivered through mobile apps to parents could be effective in improving child oral health awareness among parents. There is a need for more high-quality studies with a large number of participants to find out which features of mHealth interventions with parents could effectively be employed to reduce the prevalence of ECC. Further studies and apps should be developed based on evidence-based behaviour change techniques and incorporate features such as gamification to increase the effectiveness and engagement of the target population. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42021268331].

Mapping the evidence for monitoring fluoride exposure in community prevention programmes for oral health using nail clippings and spot urine samples: a scoping review.

BACKGROUND: There is an increased interest in identifying practical and accurate biomarkers for fluoride exposure. Due to the narrow 'dose-gap' between the benefit of caries reduction and the risk of dental fluorosis, monitoring of fluoride exposure is vital when introducing any fluoridation programme for the prevention of dental caries. This scoping review aimed to ascertain the nature and extent of the available evidence on how spot urine and nail clippings are used to measure fluoride intake/exposure, by using a unique approach of mapping the studies according to population, setting, type of study design, methodology and analytical approach in community prevention programmes. METHODS: Multiple relevant databases were searched up to July 2021 for any study designs, including randomised controlled studies, quasi-experimental studies, surveys, retrospective and prospective cohort studies, case studies, phenomenological studies, and expert opinions. RESULTS: The search retrieved 9,222 studies of which 155 met the inclusion criteria. A high proportion of the studies (25.2%) originated from Latin America and the Caribbean continent subregion. However, per country, China recorded the highest number, followed by India and Mexico. The majority (62.6%) employed a cross-sectional study design, and 65.8% combined participants from different age groups. Of the included studies, 82.6% used spot urine samples as a biomarker for assessing fluoride intake/exposure. Water fluoride concentration was reported in 66.5% of the studies with 46.6% of all included studies reporting a water fluoride concentration of > 1.2 mg/L. The methods used in assessing oral hygiene and dietary intake were not reported in 72.3% and 71.0% of the included studies, respectively. Only 35.5% of the included studies assessed the relationship between fluoride exposure and excretion. CONCLUSIONS: This review revealed a large variability in the way in which spot urine samples and/or nail clippings are used to measure fluoride exposure in different settings and situations. Particularly, there are inconsistencies in the methodologies and the analytical approaches used in assessing fluoride exposure. Therefore, there is a need for more rigorous primary research studies using standardised approaches to determine the suitability of spot urine samples and nail clipping as biomarkers for monitoring fluoride exposure.

Intrauterine and Postnatal Exposure to High Levels of Fluoride Is Associated with Motor Impairments, Oxidative Stress, and Morphological Damage in the Cerebellum of Offspring Rats.

Fluoride (F) is abundantly present on Earth and plays a beneficial role in human health. However, exposure to high doses of F can be a risk, mainly in endemic fluorosis regions. In light of this, we investigated the effects of F exposure during the intrauterine and postnatal periods of rats, in doses similar to those recommended in drinking water and the levels of F in regions with endemic fluorosis, on the offspring rats' cerebellum. Pregnant rats were divided into three groups: control (received ultrapure water only), 10 mg F/L, and 50 mg F/L for a period of 42 days (21 days gestation and 21 days lactation). At the end of the lactation period, the male pups were evaluated by behavioral tests, morphological markers, and biochemistry assays. The results pointed out that 50 mg F/L exposure during the intrauterine and lactational period of rats is capable of promoting oxidative stress in the cerebellum with a decrease in Purkinje cell density and myelin basic protein compromise, which could be associated with functional motor impairments. In addition, although 10 mg F/L exposure promoted redox alterations, it did not affect other parameters evaluated, highlighting the safe use of F in low doses.

A Scopus-Based Bibliometric Analysis of Global Research Contributions on Milk Fluoridation.

Fluoridated-milk schemes have been developed and implemented in many countries to prevent dental caries. This study aimed to evaluate the impact/influence of scientific publications, researchers, and institutions conducting research on milk fluoridation; to explore the international and inter-institutional collaboration and illustrate scientific output trends; and to pinpoint research hotspots in milk fluoridation research. This bibliometric analysis of original research articles on milk fluoridation includes all of the original articles published in peer-reviewed journals systematically extracted from the SCOPUS database. In total, 108 articles were included in this study, with a total of 11,789 citations. A majority (67.6%) of these articles were in the subject area of 'dentistry', 22.2% externally funded, 14.8% published in the journal, Caries Research, 7.4% authored/co-authored by Twetman S, 6.5% by authors from Universidad de Chile, and the UK had the highest output (24.1%). The network visualizations showed that those countries with current/past histories of implemented milk fluoridation programs were interconnected on the network visualization map, and they were predominantly the hotspots for original research on milk fluoridation. This study also identified inequalities in research outputs on the topic. With the current enormous global burden of dental caries in children, particularly in low- and middle-income countries, there is an urgent need for greater and more equitable funding of milk fluoridation research globally.

The Relationship between Fluoride Exposure and Cognitive Outcomes from Gestation to Adulthood-A Systematic Review.

Chronic exposure to high levels of fluoride may cause health concerns, including in cognitive function. This study reviewed the evidence on the association between fluoride exposure and cognitive outcomes in children from gestation up to 18 years old. A literature search was conducted for studies on pregnant women and children below 18, exposed to any source of fluoride, and assessed with a validated cognitive tool. The data were analyzed using a systematic narrative synthesis approach and by subgroup: study design, age of participants, levels of fluoride exposure and methodological quality. Our search retrieved 15,072 articles, of which 46 met the inclusion criteria. Only 6 of the studies had a longitudinal design; the remainder were cross-sectional. The levels of fluoride exposure were ≥2 mg/L in 27 studies and <2 mg/L in 13 studies; 6 studies did not report levels of fluoride exposure. Only 1 of 5 studies graded as excellent quality showed a negative association between fluoride exposure and cognitive outcomes, whereas 30 of 34 poor and fair quality studies reported a negative association. The overall evidence from this review suggests that high fluoride exposure might be associated with negative cognitive outcomes in children. However, more longitudinal studies with high methodological quality are needed on this topic.

Pharmacokinetics of fluoride in human adults: The effect of exercise.

The literature is sparse in terms of the effect of exercise on the pharmacokinetics of fluoride (F) in humans. In a 4-treatment repeated measures cross-over study, we investigated F pharmacokinetics following no exercise (control) and three exercise intensity conditions (light, moderate and vigorous) in healthy adults. At a pre-experimental session, 8 participants (18-30y) residing in a non-fluoridated-area, underwent a VO2 max test to guide the three exercise intensities for the experimental sessions. Participants were on a F-free regime one week before and throughout the four experimental weeks. We measured urinary F excretion (UFE), maximum plasma concentration (Cmax), lag time of Cmax (Tmax), and Area Under the Curve (AUC) for plasma F concentration against time, following F ingestion then no, light, moderate and vigorous exercise. Results showed no statistically significant difference in Tmax among all sessions; whereas Cmax for moderate exercise (226.2 ng/ml) was significantly higher than for no (27.0 ng/ml; p < 0.001), light (105.6 ng/ml; p = 0.016) and vigorous (94.2 ng/ml; p = 0.008) exercise. Mean AUC over 0-90 min following F ingestion was also significantly higher in moderate exercise than for no (p < 0.001), light (p = 0.004) and vigorous (p = 0.001) exercise. Mean UFE over 0-14h was 638.8, 718.7, 574.6 and 450.5  µg for no, light, moderate and vigorous exercise, with no statistically significant differences among different sessions. In conclusion, this human experimental study suggests that moderate exercise may increase the fraction of F absorbed systemically which is therefore available to produce a biological effect. Future studies should be conducted with larger samples, different age groups and using different F doses.

Biomarkers for the Assessment of Fluoride Exposure in Children.

Due to practical difficulties in quantifying fluoride exposure, the ability of various biomarkers to predict exposure has been investigated previously. However, the results are inadequate for validation of their application and usefulness. This study aimed to investigate the association between contemporary/recent biomarkers of fluoride exposure and total daily fluoride intake (TDFI) of children with large differences in fluoride exposure through drinking water. TDFI was assessed in 61 healthy 4- to 5-year-old children who provided at least 1 biomarker sample; 32 lived in a low-fluoride area (0.04 mg F/L) and 29 lived in a high-fluoride area (3.05 mg F/L). Validated questionnaires were administered to evaluate fluoride intake from diets (including water) and toothpaste ingestion. Daily urinary fluoride excretion (UFE) and fluoride concentrations in plasma, fasting whole saliva, hair, and nails (toenails/fingernails) were evaluated and related to total fluoride exposure. TDFI, UFE, and fluoride concentrations of biomarkers were statistically significantly higher in the high-fluoride area than in the low-fluoride area. There was a strong statistically significant positive correlation between TDFI and UFE (ρ = 0.756, p < 0.001); plasma fluoride concentration (ρ = 0.770, p < 0.001); and toenail fluoride concentration (ρ = 0.604, p < 0.001). The statistically significant positive correlation between TDFI and fingernail fluoride concentration (ρ = 470, p < 0.001) as well as between TDFI and fasting whole saliva fluoride concentration (ρ = 0.453, p = 0.001) was moderate, whereas it was weak between TDFI and hair fluoride concentration (ρ = 0.306, p = 0.027). In conclusion, the current study confirmed the suitability of 24-h urine samples for estimating fluoride exposure in children. The strong correlations between TDFI and fluoride in plasma and toenails also suggest these biomarkers may be considered for health risk assessments of fluoride in children who are susceptible to development of dental fluorosis.

Identifying factors to improve oral cancer screening uptake: a qualitative study.

AIMS: To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake. METHODS: Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week), irregular dental attenders living in economically deprived areas of Teesside. RESULTS: There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is 'inaccessible' on a physical and psychological level, costly, a 'tooth specialist' not a 'mouth specialist', and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer. CONCLUSIONS: The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a "health" screening setting as opposed to a "dental" setting for such checks.